Oncotarget

Research Papers:

Gga-miR-130b-3p inhibits MSB1 cell proliferation, migration, invasion, and its downregulation in MD tumor is attributed to hypermethylation

Chunfang Zhao, Xin Li, Bo Han, Lujiang Qu, Changjun Liu, Jiuzhou Song, Ling Lian and Ning Yang _

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Oncotarget. 2018; 9:24187-24198. https://doi.org/10.18632/oncotarget.24679

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Abstract

Chunfang Zhao1, Xin Li2, Bo Han1, Lujiang Qu1, Changjun Liu3, Jiuzhou Song4, Ling Lian1 and Ning Yang1

1Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China

2College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, China

3Division of Avian Infectious Diseases, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China

4Department of Animal & Avian Sciences, University of Maryland, College Park, Maryland 20742, United States

Correspondence to:

Ning Yang, email: nyang@cau.edu.cn

Ling Lian, email: lianlinglara@126.com

Keywords: gga-miR-130b-3p; methylation; proliferation; migration; invasion

Received: November 16, 2017    Accepted: February 27, 2018    Published: May 11, 2018

ABSTRACT

Marek’s disease is an oncogenic and lymphoproliferative disease of chickens caused by Marek’s disease virus. Hypermethylation or hypomethylation of CpG islands in gene promoter region are involved in the initiation and progression of carcinogenesis. In this study, we analyzed differential methylation levels of upstream region of gga-miR-130b-3p gene between Marek’s disease virus-infected tumorous and non-infected spleens. Around the upstream 1 kb of gga-miR-130b-3p gene, two amplicons were designed that covered 616 bp. There were forty-eight CpG sites in this region. CpG sites in this region presented higher methylation level in tumorous spleens compared with that in non-infected ones. There were eight CpG sites significantly hypermethylated in tumorous spleens. The expression level of three DNA methyltransferases including DNMT1, DNMT3a and DNMT3b increased and the expression level of Tet ten-eleven translocation protein 2 remarkably decreased in tumorous spleens. Hypermethylation in the upstream region of gga-miR-130b-3p gene might be a direct reason for its downregulation in MD tumorous tissues. Moreover, cell proliferation of Marek’s disease lymphoblastoid cell line MDCC-MSB1 was remarkably inhibited at 24, 36, 48, 60 and 72 h post-gga-miR-130b-3p-agomir transfection. The transwell migration assay indicated cell number of migration was significantly lower in miRNA agomir transfection group. Matrix metalloproteinases MMP2 and MMP9 are involved in tumor invasion, and their protein levels were significantly downregulated at 72 h post-miRNA-agomir transfection. Collectively, these results indicated that hypermethylation in upstream region of gga-miR-130b-3p gene contributed to its downregulation in tumorous tissues. Gga-miR-130b-3p plays an inhibitory role in lymphomatous cell transformation.


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